I have come across an issue when using IIS as the HTTP front end to Domino where XPages fails to work.
What made it obvious was all the 404 errors I was getting when looking at the Firebug console.
It turns out there is some extra configuration required on the server side to make it work, described here.
It appears that all you need to do is add the following to the
<Uri Name="/domjs/*"/> <Uri Name="/xsp/*" /> <Uri Name="/domjava/*"/>